Ambrus C M, Choi T S, Weintraub D H, Eisenberg B, Staub H P, Courey N G, Foote R J, Goplerud D, Moesch R V, Ray M, Bross I D, Jung O S, Mink I B, Ambrus J L
Semin Thromb Hemost. 1975 Jul;2(1):42-51. doi: 10.1055/s-0028-1086114.
Hyaline membrane disease (HMD) is leading single cause of death of newborn, premature infants. The "hyaline membranes" consist chiefly of fibrin. The clinical manifestation of HMD is the respiratory distress syndrome (RDS). Infants with RDS were treated with urokinase-activated human plasmin in a previous clinical trial. Survival rate was increased in the plasmin treated group as compared to the placebo recipients. However, cost and difficulty in the preparation of the enzyme made this treatment impractical. We, as well as others, have shown the premature infants lack serum plasminogen; thus they are unable to develop effective fibrinolysis and are defenseless against pulmonary fibrin deposition. Therefore, plamsinogen was tested as a possible preventive agent in RDS due to HMD. In a double blind, randomized study, infants between 1 and 2.5 kg birth weight received plasminogen or placebo shortly after birth, and were then followed for development of RDS. After 100 infants were entered into the study, the code was broken and results were evaluated to assure safety of the procedure. Among the 100 infants, 51 received placebo, 49 received plasminogen. Among the infants who received placebo, seven developed mild, and ten developed severe respiratory distress; of these ten, five died with histopathologically documented HMD. Two infants died from causes other than HMD. Among the 49 infants treated with plasminogen, 13 developed mild and three developed severe respiratory distress. There was no death due to HMD. Two deaths were due to other causes. Factors placing the infant at risk from HMD (degree of prematurity, sex, cesarean section, bleeding episodes during pregnancy, maternal diabetes) were found to be evenly distributed between control and treated groups. Since completing the first phase of the study, data of an additional 277 infants has become available. Although the code was not broken in this series, a preliminary look at mortality data in comparison with mortality data of the first series of 100 (in which the code was broken) suggests that preventive activity of plasminogen has been maintained in the second phase of the study.
透明膜病（HMD）是新生儿、早产儿死亡的主要单一原因。“透明膜”主要由纤维蛋白组成。HMD的临床表现为呼吸窘迫综合征（RDS）。在之前的一项临床试验中，患有RDS的婴儿接受了尿激酶激活的人纤溶酶治疗。与接受安慰剂的患者相比，纤溶酶治疗组的存活率有所提高。然而，酶的制备成本和难度使得这种治疗不切实际。我们以及其他人已经表明，早产儿缺乏血清纤溶酶原；因此，他们无法进行有效的纤维蛋白溶解，并且对肺纤维蛋白沉积没有抵抗力。因此，对纤溶酶原作为HMD所致RDS的一种可能预防剂进行了测试。在一项双盲、随机研究中，出生体重在1至2.5千克之间的婴儿在出生后不久接受纤溶酶原或安慰剂治疗，然后随访观察RDS的发生情况。在100名婴儿进入研究后，密码被破解，并对结果进行评估以确保该程序的安全性。在这100名婴儿中，51名接受了安慰剂，49名接受了纤溶酶原。在接受安慰剂的婴儿中，7名出现轻度呼吸窘迫，10名出现重度呼吸窘迫；在这10名重度呼吸窘迫的婴儿中，5名死于经组织病理学证实的HMD。2名婴儿死于HMD以外的原因。发现使婴儿面临HMD风险的因素（早产程度、性别、剖宫产、孕期出血事件、母亲糖尿病）在对照组和治疗组中分布均匀。自完成研究的第一阶段以来，又有277名婴儿的数据可用。尽管在这一系列研究中密码未被破解，但与第一批100名（密码已被破解）的死亡率数据相比，对死亡率数据的初步观察表明，在研究的第二阶段，纤溶酶原的预防活性得以维持。
